Cytoreductive nephrectomy in the era of immune checkpoint inhibitors: a U.S. FDA pooled analysis.

BACKGROUND: This pooled analysis of patient-level data from trials evaluated the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with or without cytoreductive nephrectomy (CN) prior to a combination of immune checkpoint inhibitor (ICI) and anti-angiogenic therapy. METHODS: Five trials of ICI plus anti-angiogenic therapy were pooled. Only patients with stage 4 at initial diagnosis were included to ensure that nephrectomy was done for cytoreductive purposes and not to previously treat an earlier stage of disease. Effect of CN prior to ICI on outcomes was evaluated using the Kaplan-Meier method and a Cox proportional hazards regression model, adjusted for age, sex, risk group, performance status, and presence of sarcomatoid differentiation. RESULTS: A total of 981 patients were included. The estimated median progression-free survival with and without nephrectomy was 15 and 11 months, respectively, and the adjusted hazard ratio (HR) was 0.71 (95% CI: 0.59 to 0.85). The estimated median overall survival with and without nephrectomy was 46 and 28 months, respectively, and the adjusted HR was 0.63 (95% CI: 0.51 to 0.77). Objective response was 60% of patients with vs 46% of patients without CN. CONCLUSIONS: Patients with mRCC with CN prior to ICI plus anti-angiogenic therapy had improved outcomes compared to patients without CN. Selection factors for CN may be prognostic and could not be fully controlled for in this retrospective analysis. Prospective determination of and stratification by prior CN may be considered when designing clinical trials to assess impact of this factor on prognosis.

A Pooled Analysis of Treatment-Free Survival in Advanced Renal Cell Carcinoma.

PURPOSE: A clinically meaningful attribute of some immune-oncology (IO) regimens is potential durable clinical benefit during a treatment-free interval. We characterize treatment-free survival (TFS) with and without ongoing toxicity in trials of frontline IO-VEGF tyrosine kinase inhibitor (TKI) combinations in patients with advanced renal cell carcinoma (aRCC). PATIENTS AND METHODS: Individual patient data were pooled by treatment arm from randomized trials submitted to the FDA evaluating IO-TKI combination in treatment-naïve aRCC with at least 30 months of median follow-up. OS, TFS, TFS with and without toxicity, and time to all protocol therapy cessation were assessed. TFS was estimated by 30-month restricted mean times defined as area between Kaplan-Meier curves for two time-to-event endpoints originating at randomization: time to all protocol therapy cessation and time to subsequent systemic therapy initiation or death. RESULTS: Three trials met criteria for analysis; 1183 pts received IO-TKI versus 1184 on control arms received TKI alone (sunitinib [SUN]). IO-TKI and SUN groups spent 9% (2.7 months [95% confidence interval (CI): 1.8, 3.5]) and 10% (2.9 months [95% CI: 2.1, 3.8]) of the 30-mo period alive and treatment-free, respectively. Mean TFS without grade ≥3 toxicity was 1.7 and 2.3 months in IO-TKI and SUN groups, respectively. CONCLUSIONS AND RELEVANCE: In this post hoc partitioned survival analysis, TFS and TFS without toxicity appeared similar in the IO-TKI group compared to the SUN group. These findings may reflect continuation of TKI until progression per protocol design in all trials and discontinuation of IO after 2 years in 2 trials.

US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer.

PURPOSE: The US Food and Drug Administration (FDA) approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET). PATIENTS AND METHODS: Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2- advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator's choice of ET (n = 239). RESULTS: In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228; hazard ratio [HR], 0.55 [95% CI, 0.39 to 0.77]; P value = .0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR, 0.90 [95% CI, 0.63 to 1.30]) in the ESR1-mut subgroup. PFS also reached statistical significance in the intention-to-treat population (ITT, N = 478; HR, 0.70 [95% CI, 0.55 to 0.88]; P value = .0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1-mut subgroup. More patients who received elacestrant experienced nausea, vomiting, and dyslipidemia. CONCLUSION: The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.

A U.S. Food and Drug Administration-pooled Analysis of Frontline Combination Treatment Survival Benefits by Risk Groups in Metastatic Renal Cell Carcinoma.

BACKGROUND: While frontline immuno-oncology/tyrosine kinase inhibitor (IO/TKI) combination therapy has established a benefit in metastatic renal cell carcinoma (mRCC), this may differ by International Metastatic RCC Database Consortium (IMDC) risk grouping. Looking at individual trials, we noted an apparently smaller magnitude of benefit for favorable-risk disease. OBJECTIVE: We aimed to assess treatment benefit by risk groupings, especially in favorable-risk, augmenting patient numbers via a pooled analysis. DESIGN, SETTING, AND PARTICIPANTS: We pooled four frontline mRCC trials of IO/TKI combinations including 3,098 patients (839 favorable-risk) with approvals from 2019 to 2021. INTERVENTION: All trials used IO/TKI combinations as the treatment option and sunitinib as the control. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We analyzed progression-free survival (PFS) and overall survival (OS) by IMDC groupings. To specifically address the favorable-risk group, we combined all others into an intermediate/poor-risk group. RESULTS AND LIMITATIONS: In this exploratory analysis adjusted for baseline covariates, IO/TKI combinations have yet to demonstrate an OS benefit in favorable-risk (hazard ratio [HR] 1.24; 95% confidence interval [CI]: 0.86, 1.78) despite demonstrating an OS benefit in the intermediate/poor-risk group (HR 0.64; 95% CI: 0.55, 0.75). In contrast, IO/TKI demonstrated a PFS benefit for both the favorable-risk (HR 0.63; 95% CI: 0.50, 0.79) and the intermediate/poor-risk (HR 0.52; 95% CI: 0.45, 0.60) group. For objective response rate, a smaller difference was observed between the combination and sunitinib arms in favorable-risk (68.2% vs 49.9%) versus intermediate/poor-risk (59.9% vs 36.5%) groups, while the difference in complete response rate was larger for favorable-risk (15.3% vs 6.0%) versus intermediate/poor-risk (9.1% vs 3.4%) groups. CONCLUSIONS: The frontline IO/TKI combination therapy benefit was shown to be greater in the intermediate/poor-risk group than in the favorable-risk group. The OS benefit observed with IO/TKI for mRCC has yet to be demonstrated for favorable-risk patients; longer follow-up is needed. PATIENT SUMMARY: Patients with intermediate/poor-risk metastatic renal cell carcinoma derive an overall survival benefit from immuno-oncology/tyrosine kinase inhibitor combinations, while data for favorable-risk remain immature.

FDA Approval Summary: Mirvetuximab Soravtansine-Gynx for FRα-Positive, Platinum-Resistant Ovarian Cancer.

On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx for treatment of adult patients with folate receptor-α (FRα)-positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic therapies. The VENTANA FOLR1 (FOLR-2.1) RxDx Assay was approved as a companion diagnostic device to select patients for this indication. Approval was based on Study 0417 (SORAYA, NCT04296890), a single-arm, multicenter trial. In 104 patients with measurable disease who received mirvetuximab soravtansine-gynx, the overall response rate was 31.7% [95% confidence interval (CI), 22.9-41.6] with a median duration of response of 6.9 months (95% CI, 5.6-9.7). Ocular toxicity was included as a Boxed Warning in the U.S. Prescribing Information (USPI) to alert providers of the risks of developing severe ocular toxicity including vision impairment and corneal disorders. Pneumonitis and peripheral neuropathy were additional important safety risks included as Warnings and Precautions in the USPI. This is the first approval of a targeted therapy for FRα-positive, platinum-resistant ovarian cancer and the first antibody-drug conjugate approved for ovarian cancer. This article summarizes the favorable benefit-risk assessment leading to FDA's approval of mirvetuximab soravtansine-gynx.

FDA Approval Summary: Lutetium Lu 177 Vipivotide Tetraxetan for Patients with Metastatic Castration-Resistant Prostate Cancer.

On March 23, 2022, the FDA approved Pluvicto (lutetium Lu 177 vipivotide tetraxetan, also known as 177Lu-PSMA-617) for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibition and taxane-based chemotherapy. The recommended 177Lu-PSMA-617 dose is 7.4 gigabecquerels (GBq; 200 mCi) intravenously every 6 weeks for up to six doses, or until disease progression or unacceptable toxicity. The FDA granted traditional approval based on VISION (NCT03511664), which was a randomized (2:1), multicenter, open-label trial that assessed the efficacy and safety of 177Lu-PSMA-617 plus best standard of care (BSoC; n = 551) or BSoC alone (n = 280) in men with progressive, PSMA-positive mCRPC. Patients were required to have received ≥1 androgen receptor pathway inhibitor, and one or two prior taxane-based chemotherapy regimens. There was a statistically significant and clinically meaningful improvement in overall survival (OS), with a median OS of 15.3 months in the 177Lu-PSMA-617 plus BSoC arm and 11.3 months in the BSoC arm, respectively (HR: 0.62; 95% confidence interval: 0.52-0.74; P < 0.001). The most common adverse reactions (≥20%) occurring at a higher incidence in patients receiving 177Lu-PSMA-617 were fatigue, dry mouth, nausea, anemia, decreased appetite, and constipation. The most common laboratory abnormalities that worsened from baseline in ≥30% of patients receiving 177Lu-PSMA-617 were decreased lymphocytes, decreased hemoglobin, decreased leukocytes, decreased platelets, decreased calcium, and decreased sodium. This article summarizes the FDA review of data supporting traditional approval of 177Lu-PSMA-617 for this indication.

FDA Approval Summary: Belzutifan for von Hippel-Lindau Disease-Associated Tumors.

On August 13, 2021, the FDA approved belzutifan (WELIREG, Merck), a first-in-class hypoxia-inducible factor (HIF) inhibitor for adult patients with von Hippel-Lindau (VHL) disease who require therapy for associated renal cell carcinoma (RCC), central nervous system (CNS) hemangioblastomas, or pancreatic neuroendocrine tumors (pNET), not requiring immediate surgery. The FDA granted approval based on the clinically meaningful effects on overall response rate (ORR) observed in patients enrolled in Study MK-6482-004. All 61 patients had VHL-associated RCC; some also had CNS hemangioblastomas and/or pNET. For VHL disease-associated RCC, ORR was 49% [95% confidence interval (CI), 36-62], median duration of response (DoR) was not reached, 56% of responders had DoR ≥12 months, and median time to response was 8 months. Twenty-four patients had measurable CNS hemangioblastomas with an ORR of 63% (95% CI, 41-81), and 12 patients had measurable pNET with an ORR of 83% (95% CI, 52-98). For these tumors, median DoR was not reached, with 73% and 50% of patients having response durations ≥12 months for CNS hemangioblastomas and pNET, respectively. The most common adverse reactions, including laboratory abnormalities, reported in ≥20% were anemia, fatigue, increased creatinine, headache, dizziness, increased glucose, and nausea. Belzutifan can render some hormonal contraceptives ineffective and can cause embryo-fetal harm during pregnancy. This article summarizes the data and the FDA thought process supporting traditional approval of belzutifan for this indication.

Impact of race on care, readmissions, and survival for patients with glioblastoma: an analysis of the National Cancer Database.

BACKGROUND: The objective of this study was to explore racial/ethnic factors that may be associated with survival in patients with glioblastoma by querying the National Cancer Database (NCDB). METHODS: The NCDB was queried for patients diagnosed with glioblastoma between 2004 and 2014. Patient demographic variables included age at diagnosis, sex, race, ethnicity, Charlson-Deyo score, insurance status, and rural/urban/metropolitan location of zip code. Treatment variables included surgical treatment, extent of resection, chemotherapy, radiation therapy, type of radiation, and treatment facility type. Outcomes included 30-day readmission, 30- and 90-day mortality, and overall survival. Multivariable Cox regression analyses were performed to evaluate variables associated with race and overall survival. RESULTS: A total of 103 652 glioblastoma patients were identified. There was a difference in the proportion of patients for whom surgery was performed, as well as the proportion receiving radiation, when stratified by race (P < .001). Black non-Hispanics had the highest rates of unplanned readmission (7.6%) within 30 days (odds ratio [OR]: 1.39 compared to White non-Hispanics, P < .001). Asian non-Hispanics had the lowest 30- (3.2%) and 90-day mortality (9.8%) when compared to other races (OR: 0.52 compared to White non-Hispanics, P = .031). Compared to White non-Hispanics, we found Black non-Hispanics (hazard ratio [HR]: 0.88, P < .001), Asian non-Hispanics (HR: 0.72, P < .001), and Hispanics (HR: 0.69, P < .001) had longer overall survival. CONCLUSIONS: Differences in treatment and outcomes exist between races. Further studies are needed to elucidate the etiology of these race-related disparities and to improve outcomes for all patients.

Risk groups of laryngeal cancer treated with chemoradiation according to nomogram scores - A pooled analysis of RTOG 0129 and 0522.

OBJECTIVES: To develop nomograms predicting overall survival (OS), freedom from locoregional recurrence (FFLR), and freedom from distant metastasis (FFDM) for patients receiving chemoradiation for laryngeal squamous cell carcinoma (LSCC). MATERIAL AND METHODS: Clinical and treatment data for patients with LSCC enrolled on NRG Oncology/RTOG 0129 and 0522 were extracted from the RTOG database. The dataset was partitioned into 70% training and 30% independent validation datasets. Significant predictors of OS, FFLR, and FFDM were obtained using univariate analysis on the training dataset. Nomograms were built using multivariate analysis with four a priori variables (age, gender, T-stage, and N-stage) and significant predictors from the univariate analyses. These nomograms were internally and externally validated using c-statistics (c) on the training and validation datasets, respectively. RESULTS: The OS nomogram included age, gender, T stage, N stage, and number of cisplatin cycles. The FFLR nomogram included age, gender, T-stage, N-stage, and time-equivalent biologically effective dose. The FFDM nomogram included age, gender, N-stage, and number of cisplatin cycles. Internal validation of the OS nomogram, FFLR nomogram, and FFDM nomogram yielded c = 0.66, c = 0.66 and c = 0.73, respectively. External validation of these nomograms yielded c = 0.59, c = 0.70, and c = 0.73, respectively. Using nomogram score cutoffs, three risk groups were separated for each outcome. CONCLUSIONS: We have developed and validated easy-to-use nomograms for LSCC outcomes using prospective cooperative group trial data.

Association between school-based tobacco retailer exposures and young adolescent cigarette, cigar and e-cigarette use.

BACKGROUND: Associations between retail tobacco availability and tobacco use have been mixed. This study examined associations between school-based retail environment exposures and current use of cigarettes, cigar products and e-cigarettes among middle school youth in Cleveland, OH. METHODS: Retailers selling tobacco products were identified using the 2015 Cleveland Food Retail Database (n=639 stores). Youth survey data were drawn from the 2016 Cleveland Youth Risk Behavior Survey, administered to all 7th/8th graders across the Cleveland Metropolitan School District (n=3778, response rate=83.0%). Past 30-day cigarette, cigar product and e-cigarette use were assessed. Student demographics, number of days walking to/from school each week and number of times youth stopped at a retailer to/from school each week were included. For each school (n=63), tobacco retail density (TRD) and proximity (TRP) to nearest retailer were calculated for each product. Multiple regression analysis assessed associations between retail exposures and youth tobacco use. RESULTS: Across all schools, 3.9%, 10.2% and 8.6% of students currently use cigarettes, cigar products and e-cigarettes, respectively, and 15.2% currently use at least one tobacco product. TRD and TRP were not associated with current use; frequency of walking to school and stopping at retailers were strongly associated with current use. CONCLUSIONS: Although TRD and TRP were not significantly associated with tobacco product use, youth who reported regularly walking to/from school or who reported stopping at a retail store before/after school were significantly more likely to be a current tobacco product user. This may be due to increased exposure to exterior and point-of-sale marketing.

Autologous Fat Transfer for Scar Prevention and Remodeling: A Randomized, Blinded, Placebo-controlled Trial.

Autologous fat transfer-also referred to as fat grafting-has been reported to provide beneficial effects to overlying scar and skin. Despite procedural frequency, there is a paucity of high-level evidence guiding the surgeon in technique, patient selection, and efficacy. METHODS: A multicenter, double-blinded, randomized, internally placebo-controlled trial was performed with an aim to qualitatively and quantitatively evaluate the impact of autologous fat transfer on the quality of overlying scar tissue. Fat-grafted scars were evaluated and compared with paired, saline-injected "control" scars. Subjective and objective metrics were evaluated in treated sites for 12 months after treatment. RESULTS: Blinded qualitative results demonstrated a statistically significant improvement in scar quality over time in fat-grafted scars. However, these improvements were not found to be statistically different from changes noted in scars treated with saline. In addition, objective metrics did not statistically differ between saline-injected and autologous fat-grafted scars. CONCLUSIONS: Our results demonstrate that autologous fat grafting can improve the qualitative profile of a scar from both the patient and observer perspectives. However, there was no difference in improvement when compared with scars that were treated with saline in a randomized and blinded fashion. These results demonstrate that any improvements in scar quality related to fat grafting are also achieved using saline and suggest that mechanisms other than cell activity may be at play. Additional randomized, blinded, placebo-controlled trials are required to either corroborate or contest the putative beneficial effect(s) of adipose tissue on scar remodeling.

Ependymoma, NOS and anaplastic ependymoma incidence and survival in the United States varies widely by patient and clinical characteristics, 2000-2016.

BACKGROUND: Ependymoma is a rare CNS tumor arising from the ependymal lining of the ventricular system. General differences in incidence and survival have been noted but not examined on a comprehensive scale for all ages and by histology. Despite the rarity of ependymomas, morbidity/mortality associated with an ependymoma diagnosis justifies closer examination. METHODS: Incidence data were obtained from the Central Brain Tumor Registry of the United States in collaboration with the Centers for Disease Control and Prevention and the National Cancer Institute, and survival data from Surveillance Epidemiology and End Results, from 2000 to 2016 for anaplastic ependymoma and ependymoma, not otherwise specified (NOS). Age-adjusted incidence rates (IRs) per 100 000 person-years were analyzed by age, sex, race, and location. Survival analysis was performed with Kaplan-Meier curves and multivariable Cox proportional hazards models. RESULTS: Incidence of anaplastic ependymoma was highest in ages 0 to 4 years. African American populations had lower incidence but had a 78% increased risk of death compared to white populations (hazard ratio [HR]: 1.78 [95% CI, 1.30-2.44]). Incidence was highest for anaplastic ependymoma in the supratentorial region. Adults (age 40+ years) had almost twice the risk of death compared to children (ages 0-14 years) (HR: 1.97 [95% CI, 1.45-2.66]). For ependymoma, NOS, subtotal resection had a risk of mortality 1.86 times greater than gross total resection ([HR: 1.86 [95% CI, 1.32-2.63]). CONCLUSIONS: African American populations experienced higher mortality rates despite lower incidence compared to white populations. Extent of resection is an important prognostic factor for survival. This highlights need for further evaluation of treatment patterns and racial disparities in the care of patients with ependymoma subtypes.

Relative survival after diagnosis with a primary brain or other central nervous system tumor in the National Program of Cancer Registries, 2004 to 2014.

BACKGROUND: The majority of reported cancer survival statistics in the United States are generated using the National Cancer Institute's publicly available Surveillance, Epidemiology, and End Results (SEER) data, which prior to 2019 represented 28% of the US population (now 37%). In the case of rare cancers or special subpopulations, data sets based on a larger portion of the US population may contribute new insights into these low-incidence cancers. The purpose of this study is to characterize the histology-specific survival patterns for all primary malignant and nonmalignant primary brain tumors in the United States using the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR). METHODS: Survival data were obtained from the NPCR (includes data from 39 state cancer registries, representing 81% of the US population). Relative survival rates (RS) with 95% CI were generated using SEER*Stat 8.3.5 from 2004 to 2014 by behavior, histology, sex, race/ethnicity, and age at diagnosis. RESULTS: Overall, there were 488 314 cases from 2004 to 2014. Overall 5-year RS was 69.8% (95% CI = 69.6%-69.9%). Five-year RS was 35.9% (95% CI = 35.6%-36.1%) for malignant and 90.2% (95% CI = 90.1%-90.4%) for nonmalignant tumors. Pilocytic astrocytoma had the longest 5-year RS (94.2%, 95% CI = 93.6%-94.6%) of all glioma subtypes, whereas glioblastoma had the shortest 5-year RS (6.1%, 95% CI = 6.0%-6.3%). Nonmalignant nerve sheath tumors had the longest 5-year RS (99.3%, 95% CI = 99.1%-99.4%). Younger age and female sex were associated with increased survival for many histologies. CONCLUSIONS: Survival after diagnosis with primary brain tumor varies by behavior, histology, and age. Using such a database that includes more than 80% of the US population may represent national survival patterns.

An independently validated survival nomogram for lower-grade glioma.

BACKGROUND: Gliomas are the most common primary malignant brain tumor. Diffuse low-grade and intermediate-grade gliomas, which together compose the lower-grade gliomas (LGGs; World Health Organization [WHO] grades II and III), present a therapeutic challenge to physicians due to the heterogeneity of their clinical behavior. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a survival nomogram for patients with newly diagnosed LGG. METHODS: Data were obtained for newly diagnosed LGG patients from The Cancer Genome Atlas (TCGA) and the Ohio Brain Tumor Study (OBTS) with the following variables: tumor grade (II or III), age at diagnosis, sex, Karnofsky performance status (KPS), and molecular subtype (IDH mutant with 1p/19q codeletion [IDHmut-codel], IDH mutant without 1p/19q codeletion, and IDH wild-type). Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using TCGA data and independently validated using the OBTS data. Models were internally validated using 10-fold cross-validation and externally validated with calibration curves. RESULTS: A final nomogram was validated for newly diagnosed LGG. Factors that increased the probability of survival included grade II tumor, younger age at diagnosis, having a high KPS, and the IDHmut-codel molecular subtype. CONCLUSIONS: A nomogram that calculates individualized survival probabilities for patients with newly diagnosed LGG could be useful to health care providers for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free online software for implementing this nomogram is provided: https://hgittleman.shinyapps.io/LGG_Nomogram_H_Gittleman/. KEY POINTS: 1. A survival nomogram for lower-grade glioma patients has been developed and externally validated.2. Free online software for implementing this nomogram is provided allowing for ease of use by practicing health care providers.

Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common and most malignant glioma. Nonglioblastoma (non-GBM) gliomas (WHO Grades II and III) are invasive and also often fatal. The goal of this study is to determine whether sex differences exist in glioma survival. METHODS: Data were obtained from the National Cancer Database (NCDB) for years 2010 to 2014. GBM (WHO Grade IV; N = 2073) and non-GBM (WHO Grades II and III; N = 2963) were defined using the histology grouping of the Central Brain Tumor Registry of the United States. Non-GBM was divided into oligodendrogliomas/mixed gliomas and astrocytomas. Sex differences in survival were analyzed using Kaplan-Meier and multivariable Cox proportional hazards models adjusted for known prognostic variables. RESULTS: There was a female survival advantage in patients with GBM both in the unadjusted (P = .048) and adjusted (P = .003) models. Unadjusted, median survival was 20.1 months (95% CI: 18.7-21.3 months) for women and 17.8 months (95% CI: 16.9-18.7 months) for men. Adjusted, median survival was 20.4 months (95% CI: 18.9-21.6 months) for women and 17.5 months (95% CI: 16.7-18.3 months) for men. When stratifying by age group (18-55 vs 56+ years at diagnosis), this female survival advantage appeared only in the older group, adjusting for covariates (P = .017). Women (44.1%) had a higher proportion of methylated MGMT (O6-methylguanine-DNA methyltransferase) than men (38.4%). No sex differences were found for non-GBM. CONCLUSIONS: Using the NCDB data, there was a statistically significant female survival advantage in GBM, but not in non-GBM.

CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2012-2016.

The Central Brain Tumor Registry of the United States (CBTRUS), in collaboration with the Centers for Disease Control and Prevention and National Cancer Institute, is the largest population-based registry focused exclusively on primary brain and other central nervous system (CNS) tumors in the United States (US) and represents the entire US population. This report contains the most up-to-date population-based data on primary brain tumors available and supersedes all previous reports in terms of completeness and accuracy. All rates are age-adjusted using the 2000 US standard population and presented per 100,000 population. The average annual age-adjusted incidence rate (AAAIR) of all malignant and non-malignant brain and other CNS tumors was 23.41 (Malignant AAAIR = 7.08, non-Malignant AAAIR = 16.33). This rate was higher in females compared to males (25.84 versus 20.82), Whites compared to Blacks (23.50 versus 23.34), and non-Hispanics compared to Hispanics (23.84 versus 21.28). The most commonly occurring malignant brain and other CNS tumor was glioblastoma (14.6% of all tumors), and the most common non-malignant tumor was meningioma (37.6% of all tumors). Glioblastoma was more common in males, and meningioma was more common in females. In children and adolescents (age 0-19 years), the incidence rate of all primary brain and other CNS tumors was 6.06. An estimated 86,010 new cases of malignant and non-malignant brain and other CNS tumors are expected to be diagnosed in the US in 2019 (25,510 malignant and 60,490 non-malignant). There were 79,718 deaths attributed to malignant brain and other CNS tumors between 2012 and 2016. This represents an average annual mortality rate of 4.42. The five-year relative survival rate following diagnosis of a malignant brain and other CNS tumor was 35.8%, and the five-year relative survival rate following diagnosis of a non-malignant brain and other CNS tumors was 91.5%.

Factors Influencing Patients' Intention to Perform Physical Activity During Hematopoietic Cell Transplantation.

OBJECTIVES: To examine theoretical and medical variables influencing a patient's intention to perform physical activity during hospitalization for hematopoietic cell transplantation (HCT). SAMPLE & SETTING: 54 patients undergoing HCT at the Seidman Cancer Center in Cleveland, Ohio. METHODS & VARIABLES: A longitudinal, prospective cohort design was used. Instruments included the Self-Report Habit Index, tailored to assess exercise habit, the Memorial Symptom Assessment Scale-Short Form, and an investigator-constructed survey of intention, attitude, control, and subjective norm toward physical activity. Descriptive statistics, univariate logistic regression, and linear regression were used. RESULTS: Intention for physical activity remained high at all time points. Previous exercise habits were not related to intention. Inverse relationships between symptom distress and the theoretical constructs that influence intention occurred at the critical time points of nadir and discharge during transplantation. IMPLICATIONS FOR NURSING: Nurses should reinforce physical activity regardless of exercise habits. Symptom distress may influence physical activity differently during the transplantation trajectory.

An independently validated nomogram for isocitrate dehydrogenase-wild-type glioblastoma patient survival.

BACKGROUND: In 2016, the World Health Organization reclassified the definition of glioblastoma (GBM), dividing these tumors into isocitrate dehydrogenase (IDH)-wild-type and IDH-mutant GBM, where the vast majority of GBMs are IDH-wild-type. Nomograms are useful tools for individualized estimation of survival. This study aimed to develop and independently validate a nomogram for IDH-wild-type patients with newly diagnosed GBM. METHODS: Data were obtained from newly diagnosed GBM patients from the Ohio Brain Tumor Study (OBTS) and the University of California San Francisco (UCSF) for diagnosis years 2007-2017 with the following variables: age at diagnosis, sex, extent of resection, concurrent radiation/temozolomide (TMZ) status, Karnofsky Performance Status (KPS), O6-methylguanine-DNA methyltransferase (MGMT) methylation status, and IDH mutation status. Survival was assessed using Cox proportional hazards regression, random survival forests, and recursive partitioning analysis, with adjustment for known prognostic factors. The models were developed using the OBTS data and independently validated using the UCSF data. Models were internally validated using 10-fold cross-validation and externally validated by plotting calibration curves. RESULTS: A final nomogram was validated for IDH-wild-type newly diagnosed GBM. Factors that increased the probability of survival included younger age at diagnosis, female sex, having gross total resection, having concurrent radiation/TMZ, having a high KPS, and having MGMT methylation. CONCLUSIONS: A nomogram that calculates individualized survival probabilities for IDH-wild-type patients with newly diagnosed GBM could be useful to physicians for counseling patients regarding treatment decisions and optimizing therapeutic approaches. Free software for implementing this nomogram is provided: https://gcioffi.shinyapps.io/Nomogram_For_IDH_Wildtype_GBM_H_Gittleman/.

Cancer collection efforts in the United States provide clinically relevant data on all primary brain and other CNS tumors.

Cancer surveillance is critical for monitoring the burden of cancer and the progress in cancer control. The accuracy of these data is important for decision makers and others who determine resource allocation for cancer prevention and research. In the United States, cancer registration is conducted according to uniform data standards, which are updated and maintained by the North American Association of Central Cancer Registries. Underlying cancer registration efforts is a firm commitment to ensure that data are accurate, complete, and reflective of current clinical practices. Cancer registries ultimately depend on medical records that are generated for individual patients by clinicians to record newly diagnosed cases. For the cancer registration of brain and other CNS tumors, the Central Brain Tumor Registry of the United States is the self-appointed guardian of these data. In 2017, the Central Brain Tumor Registry of the United States took the initiative to promote the inclusion of molecular markers found in the 2016 WHO Classification of Tumours of the Central Nervous System into information collected by cancer registries. The complexities of executing this latest objective are presented according to the cancer registry standard-setting organizations whose collection practices for CNS tumors are directly affected.